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1.
Int J Cardiol ; 330: 259-265, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33592237

RESUMO

BACKGROUND: Friedreich's ataxia (FA) is a rare autosomal recessive mitochondrial disease most commonly due to a triplet repeat expansion guanine-adenine-adenine (GAA) in the FXN gene. Cardiac disease is the major cause of death, patients with reduced left ventricular ejection fraction (LVEF) having the worse prognosis. Longitudinal strain (LS) appeared to be a better predictor of outcome than LVEF in different diseases. We compared the prognostic value of LS measured from the 4 chambers view to LVEF. METHODS: From 2003 to 2017 consecutive patients with FA were included and LS analysis was retrospectively performed. RESULTS: We studied 140 patients, with a median age of 34 (26-41) years (Q1-Q3) with age at onset of 14 (11-19) years and GAA repeats on the shorter allele of 600 (467-783) pb. Mean LS was 19.9 ± 5.0% and LVEF 64 ± 8%. After a mean follow-up of 7.4 ± 3.9 years, 14 patients died. In univariate Cox analysis, all-cause mortality was associated with: LS (HR 0.83; 95%CI, 0.75-0.91, p = 0.0002), LVEF (HR 0.30; 95%CI, 0.19-0.49, p < 0.0001), GAA repeats on the shorter allele (HR 1.29; 95%CI, 1.10-1.51, p = 0.002), age at onset (HR 0.87; 95%CI, 0.77-0.98, p = 0.018), LVSystolic Diameter (HR 1.17; 95%CI, 1.09-1.26, p < 0.0001), LVMass index (HR 1.02; 95%CI, 1.00-1.04, p = 0.027), and LVDiastolic Diameter (HR1.12; 95%CI, 1.01-1.23, p = 0.028). In multivariate analysis, LVEF was the only independent predictor of mortality (HR 0.41; 95%CI, 0.23-0.74, p = 0.0029). CONCLUSION: In FA, LS was not an independent predictor of mortality, LVEF remained the only independent predictor in the present study.


Assuntos
Ataxia de Friedreich , Adulto , Ataxia de Friedreich/diagnóstico , Ataxia de Friedreich/genética , Humanos , Prognóstico , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda
2.
Int J Cardiol ; 323: 281-284, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-32918938

RESUMO

INTRODUCTION: COVID-19 infection is commonly complicated with pro-thrombotic state and endothelial dysfunction. While several studies reported a high incidence of venous thromboembolic events. The occurrence of arterial thromboses are yet rarely described and could be underestimated. OBJECTIVES: To describe the clinical and biological characteristics of COVID-19 patients presenting with an associated arterial thromboembolic event. MATERIAL AND METHODS: We performed a retrospective multicentric study in 3 centers between France and Italy. All patients with a confirmed SARS-CoV-2 infection and arterial thromboembolic events were included in the analysis. RESULTS: From March 8th to April 25th 2020, we identified 20 patients (24 events) with arterial thromboembolic events over 209 admitted patients (9.6%) with severe COVID-19 infection. Arterial thrombotic events included acute coronary occlusions (n = 9), stroke (n = 6), limb ischemia (n = 3), splenic infarcts (n = 3), aortic thrombosis (n = 2) and occlusive mesenteric ischemia (n = 1). At the time of the event, 10/20 (50%) of patients received thromboprohylaxis, 2/20 (10%) were receiving treatment dose anticoagulation and 5/20 (25%) were receiving antiplatelet therapy. CONCLUSION: Our observations suggest that serious arterial thrombotic events might occur in Covid-19 patients. However, the exact incidence of such events and the best way to prevent them yet remains to be investigated.


Assuntos
COVID-19/complicações , Oclusão Coronária/virologia , Isquemia/virologia , Isquemia Mesentérica/virologia , Infarto do Baço/virologia , Acidente Vascular Cerebral/virologia , Trombose/virologia , Idoso , Anticoagulantes/uso terapêutico , Aorta , Extremidades/irrigação sanguínea , Feminino , França/epidemiologia , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Retrospectivos , SARS-CoV-2
3.
Ann Cardiol Angeiol (Paris) ; 69(4): 158-166, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32778388

RESUMO

BACKGROUND: Following the publication of the COMPASS trial, the European Medicines Agency has approved a regimen of combination of rivaroxaban 2.5mg twice daily and a daily dose of 75-100mg acetylsalicylic acid (ASA) for patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk of ischemic events. However, the applicability of such a therapeutic strategy in France is currently unknown. AIMS: To describe the proportion of patients eligible to COMPASS in France, their baseline clinical characteristics and the rate of major adverse cardiovascular events, using the REACH registry. METHODS: From the the REduction of Atherothrombosis for Continued Health (REACH) registry database, a large international registry of patients with, or at risk, of atherothrombosis, we analyzed patients included in France with either established CAD and/or PAD and fulfilling the inclusion and exclusion criteria of the COMPASS trial. The ischemic outcome was a composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke, and serious bleeding were defined as haemorrhagic stroke or bleeding leading to hospitalization or transfusion. RESULTS: Among more than 65000 patients enrolled in REACH, 2.012 patients were evaluable and enrolled in France. Among them, 1194 patients (59.3%) were eligible to COMPASS. The main reasons for exclusion of the COMPASS trial, were high bleeding risk (59.1%), anticoagulant use (43.4%), requirement for dual antiplatelet therapy within 1 year of an ACS or PCI (24.7%). In the "COMPASS eligible population", the rate of MACE (CV, MI and stroke) at 4 years follow-up was 13.4% [11.3-15.8], and serious bleeding was 2.5% at 4 years [1.6-3.4]. Patients with polyvascular disease (n=219) had the highest rate of MACE, compared with patients with CAD only and PAD only (19.1% [13.9-26.1] vs. 11.6% [9.1-14.8] vs 13.2% [9.2-18.8], P<0.0001, respectively). CONCLUSION: The COMPASS therapeutic strategy in France appears to be applicable to more than half of CAD or PAD patients. This population appears at high residual risk of atherothrombotic events, and patients with polyvascular disease experienced the highest rate of events.


Assuntos
Anticoagulantes/administração & dosagem , Aspirina/administração & dosagem , Doença da Artéria Coronariana/tratamento farmacológico , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação Plaquetária/administração & dosagem , Rivaroxabana/administração & dosagem , Idoso , Análise de Variância , Aterosclerose , Doença da Artéria Coronariana/epidemiologia , Esquema de Medicação , Feminino , Seguimentos , França/epidemiologia , Hemorragia/etiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Seleção de Pacientes , Intervenção Coronária Percutânea , Doença Arterial Periférica/epidemiologia , Estudos Prospectivos , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Trombose/etiologia , Fatores de Tempo , Resultado do Tratamento
4.
Ann Cardiol Angeiol (Paris) ; 66(6): 373-379, 2017 Dec.
Artigo em Francês | MEDLINE | ID: mdl-29096907

RESUMO

Coronary thrombosis remains the leading cause for cardiovascular death in France. Great advances have been made in the knowledge of the basic mechanism involved in coronary thrombogenesis and in antithrombotic treatments. They have led to substantial survival benefit after myocardial infarction and enabled development of tailored therapeutic strategies, especially for high-risk patients. Direct oral anticoagulants have now entered the game for secondary prevention after coronary thrombosis.


Assuntos
Trombose Coronária/tratamento farmacológico , Trombose Coronária/fisiopatologia , Fibrinolíticos/administração & dosagem , Medicina Integrativa , Qualidade de Vida , Administração Oral , Trombose Coronária/mortalidade , Humanos , Fatores de Risco , Resultado do Tratamento
5.
Clin Pharmacol Ther ; 100(3): 287-94, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27213804

RESUMO

Interindividual variability in platelet aggregation is common among patients treated with clopidogrel and both high on-treatment platelet reactivity (HTPR) and low on-treatment platelet reactivity (LTPR) increase risks for adverse clinical outcomes. CYP2C19 influences clopidogrel response but only accounts for ∼12% of the variability in platelet reactivity. To identify novel variants implicated in on-treatment platelet reactivity, patients with coronary artery disease (CAD) with extreme pharmacodynamic responses to clopidogrel and wild-type CYP2C19 were subjected to exome sequencing. Candidate variants that clustered in the LTPR subgroup subsequently were genotyped across the discovery cohort (n = 636). Importantly, carriers of B4GALT2 c.909C>T had lower on-treatment P2Y12 reaction units (PRUs; P = 0.0077) and residual platelet aggregation (P = 0.0008) compared with noncarriers, which remained significant after adjusting for CYP2C19 and other clinical variables in both the discovery (P = 0.0298) and replication (n = 160; PRU: P = 0.0001) cohorts. B4GALT2 is a platelet-expressed galactosyltransferase, indicating that B4GALT2 c.909C>T may influence clopidogrel sensitivity through atypical cell-surface glycoprotein processing and platelet adhesion.


Assuntos
Plaquetas/efeitos dos fármacos , Citocromo P-450 CYP2C19/genética , Galactosiltransferases/genética , Inibidores da Agregação Plaquetária/farmacologia , Ticlopidina/análogos & derivados , Adulto , Idoso , Aspirina/administração & dosagem , Clopidogrel , Doença da Artéria Coronariana/tratamento farmacológico , Quimioterapia Combinada , Exoma , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Projetos Piloto , Inibidores da Agregação Plaquetária/administração & dosagem , Ticlopidina/administração & dosagem , Ticlopidina/farmacologia
6.
Thromb Haemost ; 110(5): 1055-64, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23925438

RESUMO

A new ELISA technique has been developed to measure the vasodilator-associated stimulated phosphoprotein (VASP) platelet reactivity index (PRI) in clopidogrel-treated patients. This technique has not been evaluated in acute coronary syndrome (ACS) patients or in prasugrel-treated patients. We assessed the accuracy of ELISA-VASP to identify high on-treatment platelet reactivity (HPR) in ACS patients in comparison with established platelet function tests. Platelet reactivity was measured in 240 ACS patients treated with clopidogrel (75 or 150 mg) or prasugrel (5 or 10 mg) using flow cytometry (FC-VASP) and the ELISA-VASP technique, light transmission aggregometry (LTA) and VerifyNow-P2Y12 assay (VN-P2Y12). When using the ELISA-VASP PRI, the rate of patients with HPR in the overall ACS population was 15.5%, including a 27% rate in clopidogrel-treated patients and a 4% rate in prasugrel-treated patients. There was a strong correlation between ELISA-VASP PRI and FC-VASP PRI (r = 0.83, r2 = 0.68 p < 0.0001) with an area under the receiver-operating characteristics (ROC) curve to identify HPR (VASP-PRI >50% with FC-VASP) of 0.94, p<0.0001. The threshold of 60% for ELISA-VASP PRI provided the best accuracy (likelihood ratio= 23.67) to identify patients with HPR when compared to FC-VASP, LTA or VN-P2Y12 assays. In conclusion, ELISA-VASP is a fast, easy-to-use and specific test to identify HPR in ACS patients on thienopyridines. A 60% threshold value displays the best accuracy to identify HPR in these patients.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Anticoagulantes/administração & dosagem , Moléculas de Adesão Celular/metabolismo , Ensaio de Imunoadsorção Enzimática/métodos , Proteínas dos Microfilamentos/metabolismo , Fosfoproteínas/metabolismo , Piperazinas/administração & dosagem , Tiofenos/administração & dosagem , Ticlopidina/análogos & derivados , Síndrome Coronariana Aguda/sangue , Idoso , Separação Celular , Clopidogrel , Estudos de Viabilidade , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Plaquetária , Cloridrato de Prasugrel , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ticlopidina/administração & dosagem
7.
Int J Cardiol ; 167(3): 739-44, 2013 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-22459370

RESUMO

BACKGROUND: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) enables the estimation of myocardial infarct (MI) extent. Nevertheless, manual quantification is time consuming and subjective. We sought to assess MI volume with different quantitative methods in both acute (AMI) and chronic MI (CMI). METHODS: CMR was performed 50 ± 21 h after MI in 52 patients and was repeated 100 ± 21 days later in a subgroup of 34 patients. Then, necrosis volumes were quantified using: 1) manual delineation, 2) automated fuzzy c-means method, and 3) +2 to 6 SD thresholding approaches. Results were compared against peak values of serum Troponin I (TnI), creatine kinase (CK) and left ventricular (LV) functional parameters: LV ejection fraction (LVEF), indexed end-diastolic (EDVi), end-systolic volumes (ESVi) and the number of hypokinetic segments (NbHk). RESULTS: For CMI, quantitative evaluation of infarct size using manual, +2SD, +3 SD and fuzzy c-means provided equivalent results in terms of correlation coefficients for comparisons of MI volumes against LV function parameters (LVEF: r>0.79, p<0.0001; ESVi: r>0.82, p<0.0001, EDVi: r>0.67, p<0.0001, NbHk: r>0.54, p<0.0009). For AMI, +2SD and fuzzy c-means approaches provided higher correlations for comparisons of AMI volumes against biochemical markers (CK: r>0.79, p<0.0001,TnI: r>0.77, p<0.0001) and chronic LV function parameters (LVEF: r>0.82, p<0.0001, NbHk: r>0.59, p<0.0002). CONCLUSIONS: The fuzzy c-means and 2SD methods provided highest correlations with biochemical MI quantification as well as LV function parameters. The fuzzy c-means approach which does not require an arbitrary identification of the remote myocardium is fast and reproducible. It may be clinically useful in the evaluation of patients with MI.


Assuntos
Imagem Cinética por Ressonância Magnética/normas , Infarto do Miocárdio/diagnóstico , Estatística como Assunto/normas , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Estudos Prospectivos
8.
Int J Cardiol ; 167(6): 2646-52, 2013 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-22795712

RESUMO

BACKGROUND: To assess the impact of impaired renal function (IRF) and timing of catheterization (immediate versus delayed intervention) on outcomes in intermediate/high risk NSTE-ACS patients. METHODS: We performed a post-hoc analysis of the randomized ABOARD population to compare 1) patients with vs. without IRF and 2) the two intervention strategies in patients with IRF. A creatinine clearance <60 mL/min defined IRF. The primary endpoint was the in-hospital peak troponin I value; the secondary endpoints were a) the composite of death, myocardial infarction, urgent revascularization or recurrent ischemia (death/MI/UR/RI) and b) STEEPLE major bleeding (MB) at 1-month follow-up. RESULTS: Among the 345 patients, 75 (21.7%) had IRF. Patients with IRF were older, had more comorbidities and were at higher cardiovascular risk. Radial catheterization was predominant (84%). Among IRF patients, 37 (49%) and 38 (51%) patients were randomized to an immediate and delayed strategy, respectively. The primary and secondary endpoints rates were not different for the two comparisons. IRF was associated with more death (5.3% vs. 1.1%, p=0.043) and non-CABG MB (9.3% vs. 2.2%, p=0.001). In patients with IRF, a delayed strategy was associated with more recurrent ischemia (28.9% vs. 8.1%, p=0.021). Absence of clopidogrel pretreatment, insulin therapy and left main culprit lesion were independently associated with death/MI/UR/RI, while age and CABG surgery were related with MB. CONCLUSION: IRF is associated with worse outcomes in NSTE-ACS patients. The primary results of the ABOARD study apply also to patients with IRF in which the timing of catheterization does not impact hard outcomes.


Assuntos
Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/terapia , Cateterismo Cardíaco/métodos , Insuficiência Renal/sangue , Insuficiência Renal/terapia , Troponina I/sangue , Síndrome Coronariana Aguda/epidemiologia , Adulto , Idoso , Angioplastia Coronária com Balão/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/epidemiologia , Fatores de Tempo , Resultado do Tratamento
10.
QJM ; 105(10): 935-48, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22543683

RESUMO

Non-ST elevation (NSTE) myocardial infarction and unstable angina are the most common clinical presentations of acute coronary syndrome (ACS). Platelet activation is central to the pathogenesis of NSTE-ACS and consensus guidelines that advocate early revascularization supported by intensive antiplatelet therapy. This review examines the drugs used concurrently with aspirin as dual antiplatelet therapy in the NSTE-ACS setting. Clopidogrel represented an important therapeutic advance. However, variations in platelet response and a relatively slow onset of action compromise outcomes with clopidogrel. Evidence reviewed in this article shows that in NSTE-ACS patients, ticagrelor and prasugrel are more effective than clopidogrel and are relatively well tolerated, with an acceptable and manageable bleeding risk. The literature suggests several differences between ticagrelor and prasugrel that should allow clinicians to better tailor treatment to the patient. Head-to-head comparisons are now needed to compare directly the risks and benefits of ticagrelor and prasugrel in NSTE-ACS. Further studies also need to address other outstanding issues such as the benefits and risks of prasugrel pre-treatment and to stratify efficacy and tolerability according to diabetes mellitus (DM) and other co-morbidities. In the meantime, the issues discussed in this review should enhance clinicians' ability to optimize and individualize NSTE-ACS treatment, thereby further reducing the morbidity and mortality associated with this common cardiovascular condition.


Assuntos
Síndrome Coronariana Aguda , Adenosina/análogos & derivados , Eletrocardiografia , Piperazinas/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Tiofenos/farmacologia , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/metabolismo , Síndrome Coronariana Aguda/fisiopatologia , Adenosina/agonistas , Adenosina/metabolismo , Adenosina/farmacologia , Aspirina/farmacologia , Disponibilidade Biológica , Clopidogrel , Pesquisa Comparativa da Efetividade , Monitoramento de Medicamentos/métodos , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Humanos , Farmacovigilância , Inibidores da Agregação Plaquetária/farmacologia , Cloridrato de Prasugrel , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores Purinérgicos P2Y/metabolismo , Medição de Risco , Ticagrelor , Ticlopidina/análogos & derivados , Ticlopidina/farmacologia , Resultado do Tratamento
11.
Thromb Haemost ; 105(6): 1024-31, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21505721

RESUMO

It was the objective of this study to assess the effect of the implementation of the smoke-free legislation on haemostasis and systemic inflammation in second-hand smoking (SHS)-exposed healthy volunteers. Fibrin-rich clot properties, platelet reactivity and inflammatory biomarkers were measured before and four months following the implementation of the smoke-free legislation in gender and age-matched healthy volunteers exposed (n=23, exposed) and unexposed (n=23, controls) to occupational SHS. The primary objective was to compare fibrin-rich clot stiffness before and after implementation of the smoke-free legislation. There was 40% reduction in fibrin-rich clot stiffness following the implementation of the smoke-free legislation in SHS-exposed volunteers (17 ± 7 vs. 10.6 ± 7 dynes/cm², before and after, respectively, p=0.001). These dramatic changes were associated with a 20% reduction in fibrin fiber density (p<0.01) and a 20% reduction in clot lysis time (p=0.05). No change in fibrin properties was observed in the control group of SHS-unexposed volunteers related to the implementation of the smoke-free legislation. Of interest, neither platelet reactivity nor systemic inflammatory biomarkers were changed in either group. The smoke-free legislation is associated with significant changes in fibrin-rich clot properties toward a less thrombogenic conformation with a better fibrinolysis response while neither platelet reactivity nor systemic inflammatory biomarkers are modified. These improvements may explain the observed reduction in acute coronary syndrome following the implementation of the smoke-free legislation.


Assuntos
Síndrome Coronariana Aguda/epidemiologia , Legislação como Assunto/estatística & dados numéricos , Poluição por Fumaça de Tabaco/legislação & jurisprudência , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/imunologia , Biomarcadores/sangue , Retração do Coágulo , Fibrinólise , França , Hemostasia , Humanos , Incidência , Inflamação , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/legislação & jurisprudência , Ativação Plaquetária , Poluição por Fumaça de Tabaco/efeitos adversos
12.
Heart ; 97(11): 887-91, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21421600

RESUMO

AIM: To determine the incidence, type and possible association with mortality of major bleeding in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) treated with an invasive strategy using predominantly the radial approach and triple antiplatelet therapy. METHODS: In the multicentre randomised ABOARD Study, 352 patients with NSTE-ACS were randomised to an 'immediate percutaneous coronary intervention (PCI)' strategy or a strategy of PCI on the 'next working day'. Radial access was predominantly used in this study population. The present subanalysis evaluated the occurrence of major bleeding complications and their association with mortality at 1 month. RESULTS: Patients were treated with a triple antiplatelet therapy using high loading and maintenance doses of clopidogrel and abciximab in 99% of patients receiving PCI. The trans-radial approach was used in the vast majority of patients (84%). During the first 30 days, major bleeding complications (STEEPLE definition) occurred in 5.4% of patients (n=19), with no difference between immediate and delayed intervention. The most common bleeding complications were occult bleeding (36.8% of bleeding, n=7/19) and overt gastrointestinal bleeding (21% of bleeding, n=4/19). Patients with major bleeding had a higher peak concentration of creatinine during hospitalisation (mean±SD, 170±169 vs 97±57 µmol/l; p=0.005) and a 1-month mortality of 26.3%, much higher than patients without bleeding (0.6%, p<0.0001). Major bleeding was strongly associated with 30-day mortality (OR 50.3; 95% CI 10.1 to 249.7; p<0.0001). CONCLUSION: Despite the predominant use of the radial approach, major bleeding (essentially occult and gastrointestinal) remains a common complication, which is highly associated with mortality in patients with NSTE-ACS treated with optimal antithrombotic therapy.


Assuntos
Síndrome Coronariana Aguda/terapia , Angioplastia Coronária com Balão/métodos , Hemorragia/induzido quimicamente , Inibidores da Agregação Plaquetária/efeitos adversos , Abciximab , Idoso , Anticorpos Monoclonais/efeitos adversos , Aspirina/efeitos adversos , Clopidogrel , Quimioterapia Combinada , Feminino , Humanos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ticlopidina/efeitos adversos , Ticlopidina/análogos & derivados , Resultado do Tratamento
13.
Hamostaseologie ; 29(4): 339-48, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19882081

RESUMO

The P2Y12 receptor has proven to be a key target in the prevention of complications associated with atherosclerotic vascular disease especially in the context of acute coronary syndrome and percutaneous coronary intervention in addition to aspirin. Three generations of thienopyridines, ticlopidine, clopidogrel, and prasugrel have proven efficacy in the prevention of ischemic vascular events but with increased bleeding. The concept of individualized tailored therapy has recently emerged with the discovery of the diminished effect of some thienopyridine among carriers of the loss-of-function cytochrome (CYP) P4502C19*2 variant. Non-thienopyridine P2Y12 antagonists have also recently demonstrated that these benefits are not limited to one class of agents or may be generalizable to reversible antagonists of this receptor. Future rational use of these agents will require attention to disease and patient features to strike the optimal balance of benefit to risk.


Assuntos
Antagonistas do Receptor Purinérgico P2 , Síndrome Coronariana Aguda/prevenção & controle , Adenosina/análogos & derivados , Adenosina/uso terapêutico , Angioplastia Coronária com Balão , Aspirina/uso terapêutico , Aterosclerose/complicações , Ponte de Artéria Coronária/efeitos adversos , Hemorragia/prevenção & controle , Humanos , Piperazinas/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Cloridrato de Prasugrel , Receptores Purinérgicos P2Y12 , Acidente Vascular Cerebral/prevenção & controle , Tiofenos/uso terapêutico , Ticagrelor
14.
Eur J Neurol ; 16(8): 902-8, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19473362

RESUMO

BACKGROUND AND PURPOSE: Data on current cardiovascular event rates in patients with asymptomatic carotid artery stenosis (ACAS) are sparse. We compared the 1-year outcomes of patients with ACAS > or =70% versus patients without ACAS in an international, prospective cohort of outpatients with or at risk of atherothrombosis. METHODS: The Reduction of Atherothrombosis for Continued Health Registry enrolled patients with either > or =3 atherothrombotic risk factors or established atherothrombotic disease. We investigated the 1-year follow-up data of patients for whom physicians reported presence/absence of ACAS at the time of inclusion. RESULTS: Compared with patients without ACAS (n = 30 329), patients with ACAS (n = 3164) had higher age- and sex-adjusted 1-year rates of transient ischaemic attack (3.51% vs. 1.61%, P < 0.0001), non-fatal stroke (2.65% vs. 1.75%, P = 0.0009), fatal stroke (0.49% vs. 0.26%, P = 0.04), cardiovascular death (2.29% vs. 1.52%, P = 0.002), the composite end-point cardiovascular death/myocardial infarction/stroke (6.03% vs. 4.29%, P < 0.0001) and bleeding events (1.41% vs. 0.81%, P = 0.002). In patients with ACAS, Cox regression analyses identified history of cerebrovascular ischaemic events as most important predictor of future stroke (HR 3.21, 95% CI 1.82-5.65, P < 0.0001). CONCLUSION: Asymptomatic carotid artery stenosis was associated with high 1-year rates of cardiovascular and cerebrovascular ischaemic events. Stroke was powerfully predicted by prior cerebrovascular ischaemic events.


Assuntos
Doenças Cardiovasculares/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Idoso , Isquemia Encefálica/epidemiologia , Estenose das Carótidas/epidemiologia , Transtornos Cerebrovasculares/epidemiologia , Feminino , Humanos , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Acidente Vascular Cerebral/prevenção & controle
15.
Heart ; 95(3): 211-5, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18801782

RESUMO

OBJECTIVE: To test if delay-to-angiography (>72 hours from admission) in patients presenting with high-risk non-ST-elevation acute coronary syndromes (NSTE-ACS) is associated with adverse outcomes. DESIGN: GRACE (Global Registry of Acute Coronary Events) is a multinational registry of patients admitted with NSTE-ACS. SETTING: 14 countries with varying healthcare systems. PATIENTS: 23 396 high-risk NSTE-ACS patients with complete initial data collection entered into GRACE between 1999 and 2006 were analysed. INTERVENTIONS: Data were analysed according to delay-to-angiography and subsequent in-hospital or post-discharge adverse outcomes. MAIN OUTCOME MEASURES: Outcomes recorded included death, myocardial infarction, recurrent ischaemia, stroke, new heart failure and composite major adverse cardiovascular event (MACE) comprising death, cerebrovascular accident and myocardial infarction. Revascularisation procedures were recorded. RESULTS: 10 089 (43.1%) had no in-hospital angiography. Median delay-to-angiography was 46 hours; 3680 (34%) patients waited >72 hours. 9.3% waited >7 days before angiography. Patients waiting longest were more often older, diabetic, women and had a history of heart failure, previous myocardial infarction or hypertension. Recurrent in-hospital ischaemia (33% vs 22%), reinfarction (8.4% vs 5.0%) and heart failure (14% vs 9.1%) were more common with delayed angiography. Delayed angiography was associated with better outcomes than no angiography (MACE 18.9% vs 22.2%, p = 0.015). MACE rates within six months of admission were higher with longer delay-to-angiography and highest of all with no angiography. CONCLUSIONS: High-risk NSTE-ACS is suboptimally managed with 43% not undergoing angiography. One-third of those undergoing angiography are delayed >72 hours. Longer delays were more likely with higher risk, sicker patients. These delays were associated with adverse outcomes at six months. Very long delay was associated with lower MACE, but not mortality, compared to conservative management.


Assuntos
Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Revascularização Miocárdica , Padrões de Prática Médica , Prognóstico , Estudos Prospectivos , Qualidade da Assistência à Saúde , Radiografia , Medição de Risco , Fatores de Tempo , Resultado do Tratamento
16.
Arch Cardiovasc Dis ; 101(4): 220-5, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18654096

RESUMO

INTRODUCTION: Conflicting data exist on the risk of stent thrombosis with drug-eluting stents (DES) versus bare-metal stents (BMS). Little is known about the potential different characteristics and outcomes of DES versus BMS thrombosis. OBJECTIVE: To compare the characteristics, timing and outcomes of patients with angiographic stent thrombosis according to type of stent implanted. METHODS: The population comprised consecutive patients who underwent BMS or DES implantation (January 2003-April 2007) at Pitié-Salpêtrière Hospital. Data from patients with and without a stent thrombosis were compared to identify predictors of thrombosis. Timing of thrombosis (acute,<24 hours; subacute,<30 days; late,>30 days; very late,>1 year), clinical, angiographic and procedural characteristics, and outcomes were compared between patients with a BMS or DES thrombosis. RESULTS: A total of 3579 patients received a BMS (2815 lesions, 2318 patients) or a DES (1536 lesions, 1261 patients). Documented angiographic stent thrombosis occurred in 52 (1.4%) patients, 16 (1.3%) with a DES and 36 (1.6%) with a BMS. Rates of acute (0.1% versus 0.2%), subacute (1% versus 0.7%), late (both 0.2%) and very late (both 0.2%) thrombosis were similar in patients with BMS and DES thrombosis. Factors predictive of stent thrombosis were similar, including left ventricular failure (P<0.0001), initial percutaneous coronary intervention (PCI) for acute myocardial infarction (P<0.0001), multivessel PCI (P<0.0001), and balloon dilatation before stenting (P<0.04). Eleven (21%) cases of BMS (n=8, 22%) or DES (n=3, 19%) thrombosis arose soon after stopping antiplatelet therapy. Thirteen of 52 (25%) patients died a few hours after the event. Twenty-seven (52%) major adverse cardiac events occurred at 18 months, 7 in patients with a DES and 20 in those with a BMS (44% versus 55%, P=NS). These included 16 deaths (31%), 7 repeat PCIs and 4 myocardial infarctions. There were no independent predictive factors of death after stent thrombosis. CONCLUSIONS: BMS and DES thrombosis are similar in terms of timing of thrombosis, characteristics and outcomes, and share the same risk of late thrombosis after interruption of antiplatelet therapy.


Assuntos
Angiografia Coronária , Estenose Coronária/terapia , Trombose Coronária/diagnóstico por imagem , Stents/efeitos adversos , Angioplastia Coronária com Balão , Cateterismo , Trombose Coronária/epidemiologia , Trombose Coronária/prevenção & controle , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/terapia , Inibidores da Agregação Plaquetária/uso terapêutico , Prognóstico , Desenho de Prótese , Recidiva , Retratamento , Fatores Sexuais , Fatores de Tempo
17.
Arch Cardiovasc Dis ; 101(3): 175-80, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18477945

RESUMO

AIMS OF THE STUDY: To assess mortality in people > or =75 years of age 6 months after myocardial infarction complicated by cardiogenic shock and treated by angioplasty with complete revascularisation and optimal anti-thrombotic treatment; to compare results to those of younger patients with or without shock and to analyse predictive factors for death. MATERIALS AND METHODS: The study is based on 1011 consecutive patients with myocardial infarction admitted for primary angioplasty, subdivided into four groups by age and the presence or absence of cardiogenic shock: group 1 (<75 years of age without shock, n=733), group 2 (<75 years of age with shock, n=49), group 3 (> or =75 years of age without shock, n=208) and group 4 (> or =75 years of age with shock, n=20). These four patient groups were compared for mortality rates and predictive factors for in-hospital and 6 month mortality. RESULTS: In-hospital mortality in groups 1 to 4 was 1.7%, 30.6%, 9.1%, and 70% (p<0.0001) respectively and 6-month mortality was 3.1%, 40%, 16% and 78% (P<0.0001). By univariate analysis renal failure was a predictive factor for death at 6 months in patients without cardiogenic shock (groups 1 and 3), and left ventricular function in patients in group 2. No predictive factors were found in group 4 patients. The independent predictive factors for death at 6 months were: age >75 years of age (P<0.0003), cardiogenic shock (P<0.0001), triple vessel lesions (P<0.01) and creatinine clearance (P=0.004). CONCLUSION: Mortality after angioplasty remains high in people > or =75 years with cardiogenic shock despite all the advances in the management of myocardial infarction. These disappointing results should encourage us to assess the role of surgical revascularisation and circulatory assistance.


Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Infarto do Miocárdio/terapia , Choque Cardiogênico/mortalidade , Fatores Etários , Idoso , Feminino , França/epidemiologia , Mortalidade Hospitalar/tendências , Humanos , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Prognóstico , Fatores de Risco , Choque Cardiogênico/etiologia , Taxa de Sobrevida/tendências
18.
Arch Cardiovasc Dis ; 101(2): 81-8, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18398391

RESUMO

INTRODUCTION: Atherothrombosis is a systemic, diffuse disease associated with a high risk of cardiovascular morbidity and mortality. It is the main cause of death in Western populations, a major public health concern and its prevalence will further increase in the future. OBJECTIVES: To evaluate the rate of major vascular events at 1 year in French patients with confirmed atherothrombotic disease, recruited in the REACH international registry. METHODS: The REACH Registry has recruited 55.000 patients in 44 countries, aged at least 45 years and suffering from established atherothrombotic disease (EAD). In France, 713 investigators selected 3.514 patients with EAD between December 2003 and June 2004. Each investigator had to include 5 to 10 patients presenting after a first documented event of cerebrovascular disease (CVD), coronary artery disease (CAD) or lower limb peripheral arterial occlusive disease (PAD). The patients were followed up for 1 year with collection of major vascular events. RESULTS: Among the 3514 French patients with EAD in the REACH registry, 2.373 (68%) had documented coronary disease, 778 (22%) had an ischemic stroke and 923 (26%) had documented PAD. One quarter of CAD patients, one third of CVD patients and one half of PAD patients had another atherothrombotic disease localization. Follow-up at 1 year was documented for 3.373 patients with EAD. The 1-year event rate in patients who had EAD was a function of the number of atherothrombotic localizations: the vascular death rate was 1.8% if there was a single localization and 4.1% if there were 2 or 3 localizations, and the composite death, infarct and stroke rates were 3.8% and 7.2% respectively and 11.7% and 22.3% respectively if hospitalizations were added to the latter endpoint. CONCLUSION: The number of major vascular events during the first year is high in EAD patients although these patients were followed up on an outpatient basis and are considered to be stable. In patients with prior EAD, there was a close link between the incidence of major vascular events and the number of symptomatic arterial beds (2 or 3 sites). The risk of a major vascular event was twice as high in patients with polyvascular involvement than in those who only had one affected artery.


Assuntos
Aterosclerose/complicações , Transtornos Cerebrovasculares/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Doenças Vasculares Periféricas/epidemiologia , Sistema de Registros , Trombose/complicações , Idoso , Aterosclerose/tratamento farmacológico , Transtornos Cerebrovasculares/etiologia , Doença da Artéria Coronariana/etiologia , Feminino , França/epidemiologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/etiologia , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Prospectivos , Acidente Vascular Cerebral/epidemiologia , Trombose/tratamento farmacológico
19.
Ann Cardiol Angeiol (Paris) ; 56(6): 250-6, 2007 Dec.
Artigo em Francês | MEDLINE | ID: mdl-17963716

RESUMO

Treatment of intracoronary thrombus is well documented. Three situations should be differentiated Primary percutaneous coronary intervention for early STEMI presenters is the most frequent one. Glycoprotein IIb/IIIa inhibitors are the gold standard antithrombotic treatment with a clear mortality benefit with abciximab. Thrombectomy with simple to use devices is another attractive option for interventionalists, although there is no clear established clinical benefit. Rescue PCI following failed thrombolysis is a more complicated situation given the underlying bleeding risk that is difficult to evaluate. The second situation is when a thrombus appears during an elective PCI. Although much less frequent than primary PCI, it is more often related to a lack of identification of the risk, to an inappropriate choice of the materials or to a non-optimal upstream antithrombotic treatment. A careful identification of all potential relevant causes is the key point of the management strategy. Post-PCI rethrombosis is the third situation and probably the less frequent. However, it is the most difficult to deal with.


Assuntos
Síndrome Coronariana Aguda/terapia , Angioplastia Coronária com Balão , Trombose Coronária/terapia , Abciximab , Anticorpos Monoclonais/uso terapêutico , Fibrinolíticos/uso terapêutico , Hemorragia/prevenção & controle , Humanos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Medição de Risco , Stents , Trombectomia , Resultado do Tratamento
20.
Ann Cardiol Angeiol (Paris) ; 56 Suppl 1: S21-8, 2007 Jun.
Artigo em Francês | MEDLINE | ID: mdl-17719354

RESUMO

The clinical benefit of the combination of aspirin plus clopidogrel over aspirin alone to prevent recurrent events after acute coronary syndrome is obviously a key step of the past few years in the management of coronary artery disease. The extended benefit of this combination among patients undergoing stent implantation is another key message for clinician. The consistent benefit of the dual oral antiplatelet therapy in all clinical trials is reassuring for clinicians. However, all well designed clinical trials generate new hypothesis and unsolved clinical issues. The loading dose of clopidogrel and whether we should monitor the biological response to clopidogrel in order to improve its clinical benefit are the next clinical challenges for clinicians dealing with acute coronary syndromes. Providing adequate answers to these relevant clinical issues should improve the clinical benefit of clopidogrel. All these important points are discussed in the following manuscript.


Assuntos
Síndrome Coronariana Aguda/terapia , Angioplastia Coronária com Balão , Aspirina/uso terapêutico , Ensaios Clínicos como Assunto , Clopidogrel , Trombose Coronária/prevenção & controle , Quimioterapia Combinada , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico
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